Cargando…

Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study

BACKGROUND: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4–17 years who failed ≥1 biologic or meth...

Descripción completa

Detalles Bibliográficos
Autores principales: Hara, Ryoki, Umebayashi, Hiroaki, Takei, Syuji, Okamoto, Nami, Iwata, Naomi, Yamasaki, Yuichi, Nakagishi, Yasuo, Kizawa, Toshitaka, Kobayashi, Ichiro, Imagawa, Tomoyuki, Kinjo, Noriko, Amano, Norihito, Takahashi, Yoko, Mori, Masaaki, Itoh, Yasuhiko, Yokota, Shumpei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492394/
https://www.ncbi.nlm.nih.gov/pubmed/31039807
http://dx.doi.org/10.1186/s12969-019-0319-4
_version_ 1783415136437927936
author Hara, Ryoki
Umebayashi, Hiroaki
Takei, Syuji
Okamoto, Nami
Iwata, Naomi
Yamasaki, Yuichi
Nakagishi, Yasuo
Kizawa, Toshitaka
Kobayashi, Ichiro
Imagawa, Tomoyuki
Kinjo, Noriko
Amano, Norihito
Takahashi, Yoko
Mori, Masaaki
Itoh, Yasuhiko
Yokota, Shumpei
author_facet Hara, Ryoki
Umebayashi, Hiroaki
Takei, Syuji
Okamoto, Nami
Iwata, Naomi
Yamasaki, Yuichi
Nakagishi, Yasuo
Kizawa, Toshitaka
Kobayashi, Ichiro
Imagawa, Tomoyuki
Kinjo, Noriko
Amano, Norihito
Takahashi, Yoko
Mori, Masaaki
Itoh, Yasuhiko
Yokota, Shumpei
author_sort Hara, Ryoki
collection PubMed
description BACKGROUND: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4–17 years who failed ≥1 biologic or methotrexate received weight-tiered (< 75 kg: 10 mg/kg; 75–100 kg: 750 mg; > 100 kg: 1000 mg) intravenous abatacept at Weeks 0, 2, 4, and every 4 weeks thereafter. The study comprised a short-term period (16 weeks) and ongoing long-term period. Primary endpoint: Week 16 JIA-American College of Rheumatology criteria 30 (JIA-ACR30) response rate. Secondary endpoints/outcomes included Week 16 JIA-ACR50/70/90 response and inactive disease rates, Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), pharmacokinetics, safety, and immunogenicity. Proportions of patients achieving Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP) remission (score < 1) and minimal disease activity (MDA; score < 3.8), were among exploratory endpoints. RESULTS: All 20 patients who received study medication completed the short-term period. During the long-term period, two patients discontinued due to insufficient efficacy or patient decision. Median age and disease duration at baseline were 10.5 and 0.75 years, respectively. Week 16 JIA-ACR30 response rate (primary endpoint) was 90.0% (18/20). JIA-ACR50/70/90 response and inactive disease rates at Week 16 were 75.0% (15/20), 70.0% (14/20), 35.0% (7/20), and 25.0% (5/20), respectively. At Week 52, JIA-ACR30/50/70/90 response and inactive disease rates were observed by 88.9% (16/18), 88.9% (16/18), 83.3% (15/18), 66.7% (12/18) and 44.4% (8/18), respectively. CHAQ-DI improved after Week 12. JADAS27-CRP remission and MDA were achieved by 15.0% (3/20) and 45.0% (9/20) of patients at Week 16, and by 50.0% (9/18) and 78.0% (14/18) of patients at Week 52, respectively. The mean abatacept pre-dose serum concentration was above the target therapeutic exposure (10 μg/ml) from Week 8 through Week 16. All adverse events were of mild/moderate intensity, except for one case of severe gastroenteritis. No deaths, malignancies, or autoimmune disorders were observed. No antidrug antibodies were detected through Week 16; one patient had a positive immunogenic response during the cumulative period. CONCLUSION: Intravenous abatacept was efficacious and well tolerated in Japanese patients with active pJIA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01835470. Date of registration: April 19, 2013.
format Online
Article
Text
id pubmed-6492394
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-64923942019-05-08 Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study Hara, Ryoki Umebayashi, Hiroaki Takei, Syuji Okamoto, Nami Iwata, Naomi Yamasaki, Yuichi Nakagishi, Yasuo Kizawa, Toshitaka Kobayashi, Ichiro Imagawa, Tomoyuki Kinjo, Noriko Amano, Norihito Takahashi, Yoko Mori, Masaaki Itoh, Yasuhiko Yokota, Shumpei Pediatr Rheumatol Online J Research Article BACKGROUND: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4–17 years who failed ≥1 biologic or methotrexate received weight-tiered (< 75 kg: 10 mg/kg; 75–100 kg: 750 mg; > 100 kg: 1000 mg) intravenous abatacept at Weeks 0, 2, 4, and every 4 weeks thereafter. The study comprised a short-term period (16 weeks) and ongoing long-term period. Primary endpoint: Week 16 JIA-American College of Rheumatology criteria 30 (JIA-ACR30) response rate. Secondary endpoints/outcomes included Week 16 JIA-ACR50/70/90 response and inactive disease rates, Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), pharmacokinetics, safety, and immunogenicity. Proportions of patients achieving Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP) remission (score < 1) and minimal disease activity (MDA; score < 3.8), were among exploratory endpoints. RESULTS: All 20 patients who received study medication completed the short-term period. During the long-term period, two patients discontinued due to insufficient efficacy or patient decision. Median age and disease duration at baseline were 10.5 and 0.75 years, respectively. Week 16 JIA-ACR30 response rate (primary endpoint) was 90.0% (18/20). JIA-ACR50/70/90 response and inactive disease rates at Week 16 were 75.0% (15/20), 70.0% (14/20), 35.0% (7/20), and 25.0% (5/20), respectively. At Week 52, JIA-ACR30/50/70/90 response and inactive disease rates were observed by 88.9% (16/18), 88.9% (16/18), 83.3% (15/18), 66.7% (12/18) and 44.4% (8/18), respectively. CHAQ-DI improved after Week 12. JADAS27-CRP remission and MDA were achieved by 15.0% (3/20) and 45.0% (9/20) of patients at Week 16, and by 50.0% (9/18) and 78.0% (14/18) of patients at Week 52, respectively. The mean abatacept pre-dose serum concentration was above the target therapeutic exposure (10 μg/ml) from Week 8 through Week 16. All adverse events were of mild/moderate intensity, except for one case of severe gastroenteritis. No deaths, malignancies, or autoimmune disorders were observed. No antidrug antibodies were detected through Week 16; one patient had a positive immunogenic response during the cumulative period. CONCLUSION: Intravenous abatacept was efficacious and well tolerated in Japanese patients with active pJIA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01835470. Date of registration: April 19, 2013. BioMed Central 2019-04-30 /pmc/articles/PMC6492394/ /pubmed/31039807 http://dx.doi.org/10.1186/s12969-019-0319-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hara, Ryoki
Umebayashi, Hiroaki
Takei, Syuji
Okamoto, Nami
Iwata, Naomi
Yamasaki, Yuichi
Nakagishi, Yasuo
Kizawa, Toshitaka
Kobayashi, Ichiro
Imagawa, Tomoyuki
Kinjo, Noriko
Amano, Norihito
Takahashi, Yoko
Mori, Masaaki
Itoh, Yasuhiko
Yokota, Shumpei
Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title_full Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title_fullStr Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title_full_unstemmed Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title_short Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study
title_sort intravenous abatacept in japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase iii open-label study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492394/
https://www.ncbi.nlm.nih.gov/pubmed/31039807
http://dx.doi.org/10.1186/s12969-019-0319-4
work_keys_str_mv AT hararyoki intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT umebayashihiroaki intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT takeisyuji intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT okamotonami intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT iwatanaomi intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT yamasakiyuichi intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT nakagishiyasuo intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT kizawatoshitaka intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT kobayashiichiro intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT imagawatomoyuki intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT kinjonoriko intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT amanonorihito intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT takahashiyoko intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT morimasaaki intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT itohyasuhiko intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy
AT yokotashumpei intravenousabataceptinjapanesepatientswithpolyarticularcoursejuvenileidiopathicarthritisresultsfromaphaseiiiopenlabelstudy